CAR-T Cell Therapy, Mosunetuzumab and Polatuzumab for Treatment of Refractory/Relapsed Aggressive Non-Hodgkin's Lymphoma (NHL).

NCT05260957 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 20210828
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to test if a combination treatment of chimeric antigen receptor (CAR) T-cell therapy, Mosunetuzumab, and Polatuzumab Vedotin will result in tumor reduction.

Conditions

Refractory Non-Hodgkin Lymphoma; Relapsed Non Hodgkin Lymphoma; Aggressive Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate

  Complete Response (CR) rate will be reported as the percentage of participants achieving complete response (CR) to study treatment. Response to therapy will be assessed using Positron Emission Tomography (PET)/ Computerized Tomography (CT) scan following Lugano 2014 criteria (Cheson et al, Journal of Clinical Oncology (JCO), 2014) at 3 months (Day +90) of study treatment. For equivocal PET-CT results, biopsy will be performed after day +90 PET/CT to assess true CR or persistent lymphoma.

  3 Months

Secondary Outcomes (7)

• Overall Response Rate (ORR)

  Up to 3 months

• Progression free survival (PFS) Rate

  Up to 2 years

• Overall Survival (OS) Rate

  Up to 2 years

• Minimal residual disease (MRD) negativity

  Up to 1 year

• Duration of Response (DoR)

  Up to 2 years

Study Arms (1)

Combination CAR-T Cell Therapy, Mosunetuzumab + Polatuzumab

EXPERIMENTAL

Participants will receive study treatment in three phases: Induction Phase, CAR-T Treatment Phase and Consolidation Phase. During the Induction Phase (Days -42, through -6), participants will receive Mosunetuzumab on Days -42, -35, -28, and -7; and Polatuzumab on Day -28. On Day -6, participants will be evaluated in clinic. During the CAR-T Treatment Phase (Days -5, through Day 0), participants will receive lymphodepleting chemotherapy for three consecutive days beginning on Day -5, followed by CAR-T Cell therapy via infusion on Day 0. During the Consolidation Phase (Days +1 through +90), participants will receive Mosunetuzumab on Day +14; and combination Mosunetuzumab and Polatuzumab on Days +35, +56 and +77.

Drug: Mosunetuzumab; Drug: Polatuzumab; Biological: CAR-T Cell Therapy

Interventions

Mosunetuzumab DRUG

Induction Phase (Days -42 through -7): * 1 mg of Mosunetuzumab administered via intravenous (IV) infusion (given as per treatment guidelines) on Day -42. * 2 mg of Mosunetuzumab administered via intravenous (IV) infusion (given as per treatment guidelines) on Day -35. * 60 mg of Mosunetuzumab administered via intravenous (IV) infusion on (given as per treatment guidelines) on Days -28 and -7. Consolidation Phase (Day +1 through Day +90): 30 mg IV Mosunetuzumab administered via intravenous (IV) infusion (given as per treatment guidelines) on Days +14, +35, +56 and +77.

Also known as: BTCT4465A

Combination CAR-T Cell Therapy, Mosunetuzumab + Polatuzumab

Polatuzumab DRUG

Induction Phase (Days -42 through -7): 1.8mg/kg of Polatuzumab administered via intravenous (IV) infusion (given as per treatment guidelines) on Day -28. Consolidation Phase (Days +1 through +90): 1.8mg/kg of Polatuzumab administered via intravenous (IV) infusion (given as per treatment guidelines) on Days +35, +56 and +77.

Also known as: Polatuzumab Vedotin, RO5541077, Polivy

Combination CAR-T Cell Therapy, Mosunetuzumab + Polatuzumab

CAR-T Cell Therapy BIOLOGICAL

Participants will receive CAR-T Cell therapy via infusion on Day 0 (given as per treatment guidelines). Prior to CAR-T Cell Therapy, participants will begin receiving lymphodepleting chemotherapy on Days -5 through -3 (given as per treatment guidelines).

Also known as: Chimeric antigen receptor T-Cell Therapy

Combination CAR-T Cell Therapy, Mosunetuzumab + Polatuzumab

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologic diagnosis of:
• Diffuse large B cell lymphoma (DLBCL) not otherwise specified. Patients with primary cutaneous DLBCL of leg-type are eligible if the lymphoma expresses cluster of differentiation 19 (CD19) and if the insurance approves the CAR-T therapy. Similarly. Large cell transformation of nodal or extra-nodal marginal zone lymphoma is eligible only if the insurance allows and the disease shows strong CD19 positivity. On the other hand, post-transplant lymphoproliferative disorders (PTLD) are not allowed due to the frequently required continuation of immunosuppression to avoid organ rejection.
• Primary mediastinal B cell lymphoma (PMBCL)
• Transformed follicular lymphoma (TFL). An untransformed follicular lymphoma grade 3B will be considered on a case by case basis, since the genetic signature of grade 3B follicular lymphoma frequently resemble that of DLBCL and the large lymphomatous cells just happen to be organized in a follicular pattern. Recently, Breyanzi has an FDA indication for follicular lymphoma grade 3B.
• High grade B cell lymphoma (HGBL), other than B-lymphoblastic lymphoma
• Mantle Cell lymphoma (MCL)
• Burkitt lymphoma (BL): Although very few reports inform us about the outcome of relapsed/refractory BL, encouraging activity including CRs have been reported with CAR-T and these patients are in need because they do not have enough options available. We will need insurance approval for such enrollment.
• Additionally, the lymphoma has to be in one of the following status:
• Primary refractory which for the purpose of this study is defined as failure to obtain any response (PR or CR) after at least 3 cycles of anthracycline-based therapy or persistent disease after 6 cycles of anthracycline-based therapy as documented by a PET/CT scan that is done no later than 2 months after the last (usually the 6th) cycle of primary chemotherapy. In questionable cases, a biopsy should confirm persistence of disease as part of standard of care. In case of mantle cell lymphoma, the primary therapy if does not include an anthracycline, should include either high doses of cytarabine +/-bendamustine and an anti-CD20 antibody (usually rituximab).
• Relapsed disease that fails to respond (CR or PR) after at least 2 cycles of a platinum and/or cytarabine-based chemotherapy. For the purpose of this study, appropriate regimens include: rituximab, ifosfamide, carboplatin and etoposide (R-ICE), rituximab, dexamethasone, cytarabine, and cisplatin (R-DHAP), rituximab dexamethasone cytarabine oxaliplatin (R-DHAOx), rituximab, gemcitabine, cisplatin, and dexamethasone (R-GDP). Rituximab, gemcitabine, and oxaliplatin (R-Gem-Ox) is considered appropriate if the patient fails to obtain at least a PR after 4 doses of oxaliplatin. Patients with MCL who relapse after an anthracycline, bendamustine or cytarabine-based regimen, should have failed two salvage attempts: a molecularly targeting-based regimen including at least a Bruton's tyrosine kinase (BTK) inhibitor with or without venetoclax and a cytotoxic traditional second salvage regimen, unless the two salvage approaches are combined. For example if they fail a salvage with R-ICE + a BTK-inhibitor in combination, they are eligible without the need to be exposed to more therapy. Patients with PMBCL, they should also have failed a traditional salvage regimen and a programmed cell death protein 1 (PD-1) inhibitor-based salvage.
• Relapse after an autologous stem cell transplantation. At least 3 months should have lapsed between autologous stem cell infusion and initiation of pre-CAR-T lymphodepleting chemotherapy due to the risk of prolonged cytopenias.
• At least one of the lymphoma lesions should be measurable. For the purpose of this study an involved nodal lesion should be at least 1.5 cm in the longest diameter, while extra-nodal lymphoma lesions should have their longest diameter ≥1.0 cm
• Lymphoma cells need to be CD19 positive. In case of previous therapy with an anti-CD19 agent (including but not limited to blinatumomab, tafasitamab, loncastuximab tesirine), a new biopsy should be performed to confirm CD19 positivity.
• The performance status of the patient as measured by the Eastern Cooperative Oncology Group (ECOG) performance scale should be 0 - 2 (ECOG performance status (PS):0-2).
• The creatinine clearance as measured by the Cockcroft-Gault equation should be 50 mL/min or better (CrCl ≥ 50 mL/min).

You may not qualify if:

• Patients with EBV+DLBCL, plasmablastic lymphoma, human herpesvirus-8 (HHV-8) related B cell lymphoproliferative disorders including primary effusion lymphoma, anaplastic lymphoma kinase (ALK)+ LBCL, intravascular large B cell lymphomas, DLBCL associated with chronic inflammation, lymphomatoid granulomatosis, primary DLBCL of the CNS and T cell histiocyte rich LBCL will not be allowed because of different biology, frequent lack of CD19, difficulty in interpreting toxicity (as in the case of primary central nervous system (CNS) lymphoma) or some preliminary discouraging results with CAR-T as in the case of T-cell, histiocyte-rich large B cell lymphoma and Richter transformation of chronic lymphocytic leukemia (CLL).
• Primary CNS lymphoma or secondary CNS involvement by lymphoma.
• Similarly, patients with conditions that increase the risk of CNS toxicity will be excluded. Such conditions include but not limited to
• active seizure disorder for which an antiepileptic is taken,
• demyelinating diseases like multiple sclerosis
• history of ischemic or hemorrhagic stroke in the last 2 years
• Neurodegenerative disorders like Alzheimer and Parkinson
• Cerebral edema or hydrocephalus of any cause
• Invasive sarcoma or carcinoma in the last 3 years, except from localized basal or squamous cell carcinomas of the skin, or cervical carcinoma in situ. Localized Gleason \<7, prostate-specific antigen (PSA)\<10 prostatic adenocarcinoma T1-2N0M0 under active surveillance is allowed.
• Myocardial infarction or unstable angina or coronary revascularization within 6 months of protocol enrollment is not allowed. Stable angina that requires nitrates for pain relief is not allowed either because of concerns of hypotension during the CRS period.
• Systemic hypertension that is not controlled with maximum three antihypertensives to a level of \<160/100 precludes enrollment.
• Uncontrolled invasive infection, including fungal pneumonia, fungal sinusitis or fungal encephalitis are not allowed and should be resolved completely before enrollment. Cytomegalovirus (CMV) viremia\>200 copies/microliter or EBV viremia \> 1000 copies/microliter are not allowed unless treated completely in the case of CMV viremia and the patient then is placed on prophylactic letermovir.
• Patients with history of macrophage activation syndrome (MAS)/hemophagocytic lymphohistiocytosis (HLH) and patients with known or suspected chronic active Epstein Barr Virus infection (CAEBV).
• HIV positivity is allowed as long as the viral load of HIV-1 is less than 200 copies/microliter the last 3 months and the patient continue at least 3 antiretroviral agents during therapy.
• Chronic hepatitis B should have been controlled to hepatitis B virus (HBV) viral load \<200 copies/microliter and patients with chronic hepatitis B or even with just history of exposure to hepatitis B (hepatitis B core antibody positive but surface antigen negative) should be on suppressive therapy with entecavir, lamivudine or equivalent.

Sponsors & Collaborators

• Lazaros Lekakis: lead
• Genentech, Inc.: collaborator

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

polatuzumab vedotin; Immunotherapy, Adoptive

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Study Officials

• Lazaros Lekakis, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Robby Friedman

CONTACT

+1 (561) 7060311; rxf147@miami.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Clinical

Study Record Dates

• First Submitted: February 15, 2022
• First Posted: March 2, 2022
• Study Start: December 14, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028
• Last Updated: December 31, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)